Angiotensin II receptor blocking imidazolinone derivatives

ABSTRACT

Novel imidazolinone derivatives of formula (I), which are useful as angiotensin II antagonists, are disclosed: ##STR1##

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of application Ser. No.07/929,454, filed Aug. 14, 1992, which is a continuation-in-part ofapplication Ser. No. 07/747,023, filed Aug. 19, 1991, both abandoned.

FIELD OF THE INVENTION

This invention relates to novel substituted imidazolinone derivatives.The invention also relates to pharmaceutical compositions containing thenovel imidazolinone derivatives and pharmaceutical methods using them,alone and in conjugation with other drugs.

The compounds of this invention inhibit the action of the hormoneangiotensin II (AII) and are useful therefore in alleviating angiotensininduced hypertension. The enzyme renin acts on a blood plasmaα2-globulin, angiotensinogen, to produce angiotensin I, which is thenconverted by ACE to AII. The latter substance is a powerful vasopressoragent which has been implicated as a causative agent for producing highblood pressure in various mammalian species, such as the rat, dog, andman. The compounds of this invention inhibit the action of AII at itsreceptors on target cells and thus prevent the increase in bloodpressure produced by this hormone-receptor interaction. By administeringa compound of this invention to a species of mammal with hypertensiondue to AII, the blood pressure is reduced. The compounds of thisinvention are also useful for the treatment of congestive heart failure.Administration of a compound of this invention with a diuretic such asfurosemide or hydrochlorothiazide, either as a stepwise combined therapy(diuretic first) or as a physical mixture, enhances the antihypertensiveeffect of the compound. Administration of a compound of this inventionwith a NSAID can prevent renal failure which sometimcheme es resultsfrom administration of a NSAID.

Several peptide analogs of AII are known to inhibit the effects of thishormone by competitively blocking the receptors, but their experimentaland clinical applications have been limited by the partial agonistactivity and lack of oral absorption (M. Antonaccio, Clin. Exp.Hypertens., 1982, A4, 27-346; D. H. P. Streeten and G. H. Anderson, Jr.,Handbook of Hypertension, Clinical Pharmacology of AntihypertensiveDrugs, ed., A. E. Doyle, Vol. 5, pp. 246-271, Elsevier SciencePublisher, Amsterdam, The Netherlands, 1984).

Several non-peptide antagonists of AII have been disclosed. Thesecompounds are covered by U.S. Pat. Nos. 4,207,324; 4,340,598; 4,576,958;4,582,847; and 4,880,804; in European Patent Applications 028,834;245,637; 253,310; and 291,969; and in articles by A. T. Chiu, et al.(Eur. J. Pharm. Exp. Therap., 1988, 157, 13-21) and by P. C. Wong, etal. (J. Pharm. Exp. Therap, 1988, 247, 1-7). All of the U.S. Patents,European Patent Applications 028,834 and 253,310 and the two articlesdisclose substituted imidazole compounds which are generally bondedthrough a lower alkyl bridge to a substituted phenyl. European PatentApplication 245,637 discloses derivatives of4,5,6,7-tetrahydro-2H-imidazo[4,5-c]pyridine-6-carboxylic acid andanalogs thereof as antihypertensive agents, specifically Ca²⁺ channelblockers.

L. Chang et al., in EP O 412 594 A (filed Jul. 23, 1990) disclosesubstituted triazolinones, triazolinethiones, and triazolinimines of theformula: ##STR2## These are claimed to be antagonists of AII which areuseful for treating hypertension, congestive heart failure (CHF), andelevated intraocular pressure.

C. Bernhart et al., in WO 91/14679 (published Oct. 3, 1991) discloseheterocyclic N-substituted derivatives of the formula ##STR3## Thesecompounds are disclosed to be antagonists of AII which are useful fortreating cardiovascular disorders such as hypertension.

F. Ostermeyer et al., in EP 475,898 (published Mar. 18, 1992) discloseheterocyclic N-substituted derivatives of formula ##STR4## Thesecompounds are disclosed to be antagonists of AII which are useful fortreating cardiovascular disorders such as hypertension.

Wagner et al., in EP 0 503 162 (published Sep. 16, 1992) disclose azolederivatives of the general Formula (A) and the specific compound Example150. ##STR5## These compounds are disclosed to be antagonists of AIIwhich are useful for treating cardiovascular disorders such ashypertension.

P. Herold and P. Buhlmayer in EP 0 407 342 A2 disclose substitutedpyrimidinones, pyrimidinethiones, and pyrimidinimines of the formula:##STR6## These are claimed to be antagonists of AII which are useful fortreating hypertension.

E. Allen, et al. in EP 0 419 048 A (filed Aug. 21, 1990) disclose asimilar series of pyrimidinones which are claimed to be antagonists ofAII useful for the treatment of CHF and elevated intraocular pressure.

SUMMARY OF THE INVENTION

The present invention provides novel angiotensin II receptor antagonistsof formula (I), pharmaceutical compositions containing compounds offormula (I) and therapeutic methods using them ##STR7## wherein: R¹ isother than in the ortho position and is: ##STR8## R² is (a) H

(b) halo (F, Cl, Br, I),

(c) C₁ -C₄ alkyl,

(d) C₁ -C₄ alkoxy,

(e) C₁ -C₄ acyloxy,

(f) C₁ -C₄ alkylthio,

(g) C₁ -C₄ alkylsulfinyl,

(h) C₁ -C₄ alkylsulfonyl,

(i) hydroxy (C₁ -C₄) alkyl,

(j) aryl (C₁ -C₄) alkyl,

(k) --CO₂ H,

(l) --CN,

(m) tetrazol-5-yl,

(n) --CONHOR¹³,

(o) --SO₂ NHR²³,

(p) --NH₂,

(q) C₁ -C₄ alkylamino,

(r) C₁ -C₄ dialkylamino,

(s) --NHSO₂ R²⁴,

(t) --NO₂,

(u) furyl,

(v) aryl,

wherein aryl is phenyl optionally substituted with one or twosubstituents selected from the group consisting of halo, C₁ -C₄ alkyl,C₁ -C₄ alkoxy, --NO₂, --CF₃, C₁ -C₄ alkylthio, --OH, --NH₂, C₁ -C₄alkylamino, C₁ -C₄ dialkylamino, --CN, --CO₂ H, --CO₂ CH₃, --CO₂ CH₂CH₃, --CO₂ benzyl;

R³ is

(a) H,

(b) halo,

(c) C₁ -C₄ alkyl,

(d) C₁ -C₄ alkoxy,

(e) C₁ -C₄ alkoxyalkyl;

R⁴ is

(a) --CN,

(b) --NO₂,

(c) --CO₂ R¹¹ ;

R⁵ is

(a) H,

(b) C₁ -C₆ alkyl,

(c) C₃ -C₆ cycloalkyl,

(d) C₂ -C₄ alkenyl,

(e) C₂ -C₄ alkynyl;

R⁶ is

(a) C₁ -C₁₀ alkyl,

(b) C₃ -C₈ alkenyl,

(c) C₃ -C₈ alkynyl,

(d) C₃ -C₈ cycloaklyl

(e) C₄ -C₈ cycloalkenyl,

(f) C₄ -C₁₀ cycloalkylalkyl,

(g) C₅ -C₁₀ cycloalkylalkenyl,

(h) C₅ -C₁₀ cycloalkylalkynyl,

(i) --(CH₂)_(s) Z² (CH₂)_(m) R⁵,

(j) phenyl, optionally substituted with 1-2 substituents selected fromthe group of halo, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, nitro, amino, hydroxyand benzyloxy;

(k) benzyl, optionally substituted on the phenyl ring with 1-2substituents selected from the group of halo, C₁ -C₄ alkyl, C₁ -C₄alkoxy or --NO₂ ;

R⁷, R⁸, R⁹, and R¹⁰ are independently chosen from

(a) H,

(b) C₁ -C₈ alkyl unsubstituted or substituted by one or more halogen,

(c) C₃ -C₆ cycloalkyl,

(d) NO₂,

(e) CN,

(f) CONR¹⁵ R¹⁶

(g) CO₂ R¹⁷,

(h) OR¹⁸,

(i) (CH₂)_(n) CONR¹⁵ R¹⁶ where n is 1-4,

(j) (CH₂)_(n) CO₂ R¹⁷ where n is 1-4,

(k) (CH₂)_(n) OR¹⁸ where n is 1-4,

(l) aryl, wherein aryl is as defined above,

(m) CH₂ aryl, wherein aryl is as defined above;

R⁷ and R⁸ taken together can be S, O, NR¹⁹ or CR¹¹ R¹² ;

R⁹ and R¹⁰ taken together can be --(CH₂)_(t) --, --(CH₂)_(n) X(CH₂)_(m)--, or NR¹⁹ ;

R⁹ and R¹⁰ taken together can be S or O provided that R⁷ and R⁸independently or when taken together are not C₁ -C₈ alkyl unsubstitutedor C₁ -C₈ alkyl substituted with a substituent selected from the groupof halogen, C₃ -C₆ cycloalkyl, (CH₂)_(n) OR¹⁸, aryl, wherein aryl isdefined as above or --(CH₂)_(t) --;

R⁷ and R⁹ can be taken together to form an imide --CONR²² CO--;

R⁷ and R⁹ taken together can be --CH₂ NR²² CH₂ --, provided that bothR⁷, R⁸ and R⁹, R¹⁰ are not S, O, NR¹⁹ or --(CH)_(t) --;

(n) (3-indolyl)methyl,

(o) (4-imidazolyl)methyl;

R¹¹ and R¹² are independently

(a) H,

(b) C₁ -C₆ alkyl,

(c) C₃ -C₆ cycloalkyl,

(d) phenyl,

(e) benzyl,

(f) R¹¹ and R¹² when taken together can be --CH_(n) XCH_(n) --;

R¹³ is

(a) H,

(b) methyl,

(c) benzyl;

R¹⁴ is

(a) --CO₂ H,

(b) --CH₂ CO₂ H,

(c) --C(CF₃)₂ OH,

(d) --CONHNHSO₂ CF₃,

(e) --CONHOR¹³,

(f) --CONHSO₂ R²⁴,

(g) --CONHSO₂ NHR²³,

(h) --C(OH)R²³ PO₃ H₂,

(i) --NHCOCF₃,

(j) --NHCONHSO₂ R²⁴,

(k) --NHPO₃ H₂,

(l) --NHSO₂ R²⁴,

(m) --NHSO₂ NHCOR²⁴,

(n) --OPO₃ H₂,

(o) --OSO₃ H,

(p) --PO(OH)R²³,

(q) --PO₃ H₂

(r) --SO₃ H,

(s) --SO₂ NHR²³,

(t) --SO₂ NHCOR²⁴,

(u) --SO₂ NHCONHR²³, ##STR9## R¹⁵ and R¹⁶ are independently (a) H,

(b) C₁ -C₆ alkyl,

(c) aryl, wherein aryl is as defined above,

(d) aryl (C₁ -C₄) alkyl, wherein aryl is as defined above;

R¹⁵ and R¹⁶ when taken together can constitute a

(a) piperidine ring,

(b) morpholine ring,

(c) piperazine ring, optionally N-substituted with C₁ -C₆ alkyl, phenylor benzyl;

R¹⁷ is

(a) H,

(b) C₁ -C₆ alkyl,

(c) phenyl,

(d) benzyl;

R¹⁸ is

(a) H,

(b) C₁ -C₆ alkyl,

(c) phenyl,

(d) benzyl;

R¹⁹ is

(a) H,

(b) OR¹⁸

(c) C₁ -C₆ alkyl,

(d) aryl,

(e) C₁ -C₆ alkyl aryl, wherein aryl is as defined above,

(f) NR²⁰ R²¹ ;

R²⁰ and R²¹ are independently

(a) H,

(b) C₁ -C₆ alkyl,

(c) phenyl,

(d) benzyl,

R²⁰ and R²¹ taken togther can constitute a

(a) piperidine ring,

(b) morpholine ring,

(c) piperazine ring, optionally N-substituted with C₁ -C₆ alkyl, phenylor benzyl;

R²² is

(a) H,

(b) C₁ -C₆ alkyl,

(c) benzyl;

R²³ is

(a) H,

(b) C₁ -C₅ alkyl,

(c) aryl,

(d) --CH₂ --aryl, where aryl is defined as above,

(e) heteroaryl;

wherein heteroaryl is an unsubstituted, monosubstituted or disubstituted5- or 6-membered aromatic ring which can optionally contain from 1 to 3heteroatoms selected from the group consisting of O, N, and S andwherein the substituents are members selected from the group consistingof --OH, --SH, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, --CF₃, halo, --NO₂, --CO₂ H,--CO₂ CH₃, --CO₂ -benzyl, --NH₂, C₁ -C₄ alkylamino, or C₁ -C₄dialkylamino;

R²⁴ is

(a) aryl, where aryl is as defined above,

(b) C₃ -C₇ cycloalkyl,

(c) C₁ -C₄ perfluoroalkyl,

(d) C₁ -C₄ alkyl optionally substituted with a substituent selected fromthe group consisting of aryl as defined above, heteroaryl as definedabove, --OH, --SH, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₁ -C₄ alkylthio, --CF₃,halo, --NO₂, --CO₂ H, --CO₂ CH₃, --CO₂ -benzyl, --NH₂, C₁ -C₄alkylamino, C₁ -C₄ dialkylamino, or --PO₃ H₂,

(e) C₁ -C₄ alkoxy optionally substituted with a substituent selectedfrom the group consisting of aryl as defined above, heteroaryl asdefined above, --OH, --SH, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₁ -C₄alkylthio, --CF₃, halo, --NO₂, --CO₂ H, --CO₂ CH₃, --CO₂ -benzyl, --NH₂,C₁ -C₄ alkylamino, C₁ -C₄ dialkylamino, --PO₃ H₂, or

(f) heteroaryl where heteroacryl is as defined above;

X is

(a) S,

(b) O,

(c) --NR²² --;

Z is

(a) --O--,

(b) --S--,

(c) --NR¹¹ --;

m is 1 to 5;

n is 1 to 4;

s is 0 to 5;

t is 2 to 5;

or a pharmaceutically acceptable salt thereof.

Preferred compounds of this invention are those of formula (I) wherein

R¹ is in the para position and is ##STR10## R⁶ is (a) C₁ -C₁₀ alkyl,unsubstituted or substituted with one or more halogen

(b) C₃ -C₁₀ alkenyl,

(c) C₃ -C₁₀ alkynyl,

(d) C₃ -C₈ cycloalkyl,

(e) phenyl, optionally substituted with 1-2 substituents selected fromthe group of halo, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, nitro, amino, hydroxyand benzyloxy;

(f) benzyl, optionally substituted on the phenyl ring with one or twosubstitutents selected from the group consisting of halo, C₁ -C₄ alkyl,C₁ -C₄ alkoxy and --NO₂ ;

R⁷, R⁸, R⁹, R¹⁰ are independently

(a) H,

(b) C₁ -C₈ alkyl unsubstituted or substituted by one or more halogen,

(c) C₃ -C₆ cycloalkyl

(d) aryl, wherein aryl is as defined above;

R⁷ and R⁸ taken together can be S, O, NR¹⁹ or CR¹¹ R¹² ;

R⁹ and R¹⁰ taken together can be --(CH₂)_(t) --, --(CH₂)_(n) X(CH₂)_(m)or NR¹⁹, provided that R⁹ and R¹⁰ are not taken together to form NR¹⁹ or--(CH₂ ) _(t) --, when R⁷ and R⁸ are taken together to form S, O, NR¹⁹ ;

R⁹ and R¹⁰ taken together can be S or O provided that R⁷ and R⁸independently or when taken together are not C₁ -C₈ alkyl unsubstitutedor C₁ -C₈ alkyl substituted with a substituent selected from the groupof halogen, C₃ -C₆ cycloalkyl, (CH₂)_(n) OR¹⁸, aryl, wherein aryl isdefined as above or --(CH₂)_(t) --;

R¹⁴ is

(a) --CO₂ H,

(b) --CONHSO₂ R²⁴,

(c) --NHCONHSO₂ R²⁴,

(d) --NHSO₂ R²⁴,

(e) --NHSO₂ NHCOR²⁴,

(f) --PO₃ H₂,

(g) --SO₃ H,

(h) --SO₂ NHR²³,

(i) --SO₂ NHCOR²⁴,

(j) --SO₂ NHCONHR²³, ##STR11## or a pharmaceutically acceptable saltthereof.

Still more preferred are compounds of the above preferred scope formula(I) wherein

R² is

(a) H

(b) halo,

(c) C₁ -C₄ alkyl,

(d) C₁ -C₄ alkoxy;

R⁶ is

(a) C₁ -C₇ alkyl,

(b) C₃ -C₄ alkenyl,

(c) C₁ -C₄ alkynyl;

(d) phenyl, optionally substituted with 1-2 substituents selected fromthe group of halo, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, nitro, amino, hydroxyand benzyloxy;

R¹⁴ is

(a) --CO₂ H,

(b) --CONHSO₂ R²⁴,

(c) --NHCONHSO₂ R²⁴,

(d) --NHSO₂ R²⁴,

(e) --NHSO₂ NHCOR²⁴,

(f) --SO₂ NHR²³,

(g) --SO₂ NHCOR²⁴,

(h) --SO₂ NHCONHR²³, ##STR12## or a pharmaceutically acceptable saltthereof.

Most preferred due to their activity as angiotensin II antagonists arecompounds of the more preferred scope wherein

R¹ is ##STR13## or a pharmaceutically acceptable salt thereof.

Illustrative of the most preferred compounds of the invention are thefollowing:

1,5-dihydro-5,5-dimethyl-2-propyl-1-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dimethyl-2-butyl-1-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dimethyl-2-butenyl-1-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-ditrifluoromethyl-2-propyl-1-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dicyclopropyl-2-propyl-1-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dimethyl-2-butenyl-1-[(2'-(N-((phenylsulfonyl)carboxamido)biphen-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dimethyl-2-propyl-1-[(2'-(trifluoromethanesulfonylamido)biphen-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dimethyl-2-propyl-1-[(2'-(N-benzoylsulfonamido)biphen-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dimethyl-2-propyl-1-[(2'-(N-(4-chloro)benzoylsulfonamido)biphen-4-yl)methyl]-4H-imidazol-4-one

1,5-diazaspiro-((4.5))-deca-3-ene-2-propyl-1-[(2'-(1H-tetrazol-5-yl)-(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

3,5-dihydro-5-(1-phenylethylidene)-2-propyl-3-[(2'(1H-tetrazol5yl)(1,1'-biphenyl)4yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dimethyl-2-propyl-1-[(2'-(N-hexanoylsulfonamido)biphen-4-yl)methyl]-4H-imidazol-4-one

1,5-dihydro-5,5-dimethyl-2-propyl-1-[(2'-(N-trifluoroacetylsulfonamido)biphen4yl)methyl]-4H-imidazol-4-one

4'-(1,5-dihydro-5,5-dimethyl-2-propyl-4H-imidazol-4-one-1-yl-methyl)3'-methyl(1,1'-biphenyl-2-yl)sulfonylcarbamic acid n-butyl ester

4'-(3,5-dihydro-5(1-phenylethyledene)-2-propyl-4H-imidazol-4-one-3yl-methyl)-3'-methyl(1,1'-biphenyl-2-yl)sulfonylcarbamic acid n-butyl ester

4'-(1,5-dihydro-5,5-dimethyl-2-propyl-4H-imidazol-4-one-1-yl-methyl)-3'-methyl(1,1'-biphenyl-2-yl)sulfonylcarbamic acid (2-methylpropyl)ester

4'-(1,5-dihydro-5,5-dimethyl-2-butyl-4H-imidazol-4-one-1-yl-methyl)-3'-methyl(1,1'-biphenyl-2-yl)sulfonylcarbamic acid n-butyl ester

4'-(1,5-dihydro-5,5-dimethyl-2-butyl-4H-imidazol-4-one-1-yl-methyl)-3'-methyl(1,1'biphenyl-2-yl)sulfonylcarbamic acid (2-methylpropyl)ester

4'-(1,5-dihydro-5,5-ditrifluoromethyl-2-propyl-1-4H-imidazol-4-one-1-yl-methyl)-3'-methyl(1,1'-biphenyl-2-yl)sulfonylcarbamic acid (2-methylpropyl)ester

4'-(1,5-dihydro-5,5-dicyclopropyl-2-propyl-1-4H-imidazol-4-one-1-yl-methyl)-3'-methyl(1,1'-biphenyl-2-yl)sulfonylcarbamic acid n-butyl ester.

Pharmaceutically suitable salts include both the metallic (inorganic)salts and organic salts; a list of which is given in Remington'sPharmaceutical Sciences, 17th Edition, p. 1418 (1985). It is well knownto one skilled in the art that an appropriate salt form is chosen basedon physical and chemical stability, flowability, hydroscopicity, andsolubility. Preferred salts of this invention for reasons cited aboveinclude potassium, sodium, calcium, and ammonium salts.

DETAILED DESCRIPTION

Synthesis

The compounds of formula (I) may be prepared using the reactions andtechniques described in this section. The reactions are performed insolvent suitable to the reagents and materials employed and suitable forthe transformation being effected. It is understood by those skilled inthe art of organic synthesis that the functionality present on theimidazole and other portions of the molecule must be consistent with thechemical transformations proposed. This will frequently necessitatejudgment as to the order of synthetic steps, protecting groups required,deprotection conditions and activation of a benzylic position to enableattachment to nitrogen on the imidazole nucleus. Throughout thefollowing section, not all compounds of formula (I) falling into a givenclass may necessarily be prepared by all the methods described for thatclass. Substituents on the starting materials may be incompatible withsome of the reaction conditions required in some of the methodsdescribed. Such restrictions to the substituents which are compatiblewith the reaction conditions will be readily apparent to one skilled inthe art and alternative methods described must then be used. Thecompounds of this application that have a chiral center may be resolvedinto the pure or partially pure optical isomers by any of theappropriate procedures known to those skilled in the art.

The compounds of the present invention can be prepared by reaction of asulfonamide of Formula 2 with an acylating reagent such as an acylhalide or acyl imidazole, or an alkyl chroroformate, or a carbamoylatingreagent such as an isocyanate, (Scheme 1). Alcohol exchange can also beperformed on compounds of Formula 36 by heating with excess of thedesired alcohol to give new compounds within the present invention. Thesulfonamides (2) can be prepared as described in European ApplicationEP479,479, which is hereby incorporated by reference, and as shown inScheme 1a. ##STR14##

The alkylation produces a mixture of the two regioisomers using ethersodium hydride or potassium carbonate as base. The N¹ regioisomer is themajor and the N³ is the minor products. These two isomers can beseparated and purified using conventional separation techniques such aschromatography or crystallization. In those cases where separation ofregioisomers is difficult by conventional techniques, the mixture can betransformed into suitable derivatives that can be separated by usualseparation methods. They possess distinct physical and biologicalproperties. ##STR15##

The biphenyl intermediates of formula 6 can be prepared as described inEuropean Patent Applications EP479,479 and references therein, or asshown in Scheme 2. The boronic acid (4) may be prepared by lithiation ofsulfonamide (4a) followed by treatment with triisopropyl borate andhydrolysis as shown in Scheme 2. ##STR16##

The starting imidazolinones are readily available by any number ofstandard methods. For example, imidazolinone of formula 1 can beprepared as shown in Scheme 3. The amino nitrile 7 is readily obtainablefrom aldehydes and ketones via the Strecker Synthesis and variousmodifications thereof (R⁷ =R⁸ =CF₃, Y. V. Zeifman, N. P. Gambaryan, I.L. Knunyants, Dokl. Acad. Nauk. S.S.S.R., 153, 1334, 1963). Treatment ofthe amino nitrile with triethyl amine and one equivalent of theappropriate acyl or aroyl chloride 8 in methylene chloride at roomtemperature overnight, gives the corresponding amidonitrile 9.Alternatively, the nitrile can be made following the procedure describedin German patent disclosure DE3704100A1. The nitrile can be hydrolyzedto the diamide 10 using standard procedures such as treatment withhydrochloric acid followed by ammonium hydroxide. Treatment of thediamide with 1N sodium hydroxide as described in E. Mohr, J. Pract.Chem., 81, 49, 1910, gives the imidazolinone 1. ##STR17##

Alternatively, imidazolinones of formula 1 can also be prepared as shownin Scheme 4. Treatment of the amino acid 11 with tert-butylpyrocarbonate 12 with two or more equivalents of base gives the BOC(tertbutyloxycarbonyl) protected amino acid 13, M. Bodanszky and A.Bodanszky, The Practice of Peptide Chemistry, 1984. The protected aminoamide 14 can be synthesized from the active ester followed by ammonia.Deprotection using HCl gas gives the amino amide hydrochloride 15.Treatment with two or more equivalents of base and the appropriate acylor aroyl chloride gives the diamide 10 which can be cyclized bytreatment with 1N sodium hydroxide as described above. ##STR18##

Likewise, compound 10 may be obtained by reacting amino acid with therequisite acid chloride by either a Schotten-Baumann procedure, orsimply stirring in a solvent such as methylene chloride in the presenceof base such as sodium bicarbonate, pyridine or triethyl amine followedby coupling reaction with ammonia via a variety of amide or peptideforming reactions such as DCC coupling, azide coupling, mixed anhydridesynthesis or any other coupling procedure familiar to one skilled in theart.

The use of 1-amino-1-cycloalkylcarboxylic acids in the above procedureprovides the imidazolinone starting materials for the preparation of thespiro-substituted imidazolinones of formula (1).

Imidazolinones of formula 1 can also be prepared following the proceduredescribed in Japanese Patent disclosure JP 58055467.

Imidazolinones of formula 1 wherein R⁷ and R⁸ are both phenyl can beprepared as shown in Scheme 5 by reaction of benzil 16 with alkyl oraryl amidine hydrochloride 17, A. W. Cox, Org. Syn., 1, 5, R. T. Boere,R. T. Oakley, R. W. Reed, J. Organomet. Chem., 331, 161, 1987, in thepresence of base such as 1N sodium hydroxide, G. Rio and A. Rajon, Bull.Soc. Chim. France, 543, 1958 and references therein. ##STR19##

The imidazoline thiones of formula 19 can be prepared by treatment ofthe requisite alkylated imidazolinone 18 with Lawesson's reagent orphosphorus pentasulfide as described in M. P. Cava and M. I. Levinson,Tetrahedron, 41, 5061, 1985 (Scheme 6). ##STR20##

Compounds of formula 20 can be prepared by treatment of the requisitealkylated imidazolinone 18 with Meerwein's reagent, H. Meerwein, Org.Syn., 5, 1080, 1973, in ether followed by treatment with ammonia, alkylor aryl amines, hydroxyl amines or hydrazines, as shown in Scheme 7. Theaminals of formula 21 can be prepared by reducing the requisite iminesof formula 20 with lithium aluminum hydride in tetrahydrofuran or sodiumborohydride in ethanol for 1 to 24 hours at room temperature to theboiling temperature of solvent. Alternatively, compounds of formula 20can be prepared by alkylating the imines of formula 22 with therequisite benzyl halides 2. ##STR21##

The imines of formula 22 can be prepared from base catalyzed cyclizationreaction of the amido amidine 23 which was prepared by treatment of theamido nitrile of formula 9 with anhydrous HCl in ethanol followed byammonia (Scheme 8). ##STR22##

As shown in Scheme 9, the imidazoline thione of formula 24 wherein R⁷ orR⁸ cannot be hydrogen can be prepared by treating the requisiteimidazolinone 1 with Lawesson's reagent or phosphorus pentasulfide asdescribed in M. P. Cava and M. I. Levinson, Tetrahedron, 41, 5061, 1985.Alkylation using base such as sodium hydride followed by alkyl halidesuch as methyl iodide followed by oxidation with meta-chloroperbenzoicacid (MCPBA) gives the (methyl sulfonyl)imidazole 25 which can besubjected to nucleophilic displacement reaction with nucleophiles suchas cyanide to give cyanoimidazoles 26. The cyanoimidazoles can beselectively reduced to give the cyanoimidazoline 27. The nitrile groupcan be further elaborated into other functional groups such ascarboxylic acid 28, amidine 29, by methods familiar to one skilled inthe art. ##STR23##

The cyanoimidazoline 30 can be hydrolyzed and cyclized using standardprocedure such as treatment with hydrochloric acid and ethanol to formthe cyclic imide (31, Scheme 10). Alkylation using base such as sodiumhydride followed by alkyl halide gives the cyclic imide derivative 32which can be reduced with reducing agent such as diisobutylaluminumhydride (DIBAL-H) or lithium aluminum hydride to give compound 33.##STR24##

As shown in Scheme 11, the hydroxy imidazoline 34 can be prepared byreduction of the requisite imidazolinone wherein R⁷ and/or R⁸ cannot behydrogen with reducing agents such as DIBAL-H. The hydroxyl group may bereadily converted to the ethers 35 by a variety of procedures such astreatment with potassium t-butoxide, sodium hydride or the like insolvent such as dimethyl formamide followed by treatment with alkylhalide, tosylate or mesylate at room temperature for 1-24 hours. Thehydroxyl group wherein R⁷ and/or R⁸ is not polyfluoro or perfluoroalkylmay be acylated to give esters of formula 38. Acylation can be achievedwith 1-3 equivalents of an acyl halide or an anhydride in a solvent suchas diethyl ether, methylene chloride in the presence of base such astriethyl amine or pyridine. The hydroxy imidazoline can be heated ortreated with formic acid to form the acyliminium ion which can betreated with nucleophiles such as cyanide to form cyanoimidazoline 36 oramines to form aminoimidazoline 37. ##STR25##

Imidazolinones of formula 1 wherein R⁷ and R⁸ taken together are CR¹¹R¹² can be prepared as described by J. Lamboy, J. Am. Chem. Soc., 76,133, 1954, A. Jain and A. K. Mukerjee, J. Indian Chem. Soc., 65, 141,1988, H. Lehr et al., J. Org. Chem., 75, 3640, 1953. Scheme 12 shows thereaction of alkyl or aryl imidate 39 with glycine ethyl esterhydrochloride 40 and a ketone 41 in refluxing toluene and tertiary basesuch as triethyl amine to give the desired imidazolinone. The imidatehydrochloride salt can be prepared by following McElvain, J. Am. Chem.Soc., 64, 1825, 1942. Treatment with base such as K₂ CO₃ in organicsolvent such as methylene chloride gives the free base.

The compounds of this invention and their preparation can be understoodfurther by the following examples which do not constitute a limitationof the invention. In these examples, unless otherwise indicated, alltemperatures are in degrees centigrade and pans and percentages are byweight.

EXAMPLE 1 Preparation of1,5-Dihydro-5,5-dimethyl-2-propyl-1-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

PART A: Preparation of 2-N-Butyramido-isobutyronitrile

Butyryl chloride (23.0 g, 0.22 mol) was added dropwise to a cooledmixture of 2-amino-isobutyronitrile (16.8 g, 0.20 mol) and triethylamine (25 g, 0.25 mol) in methylene chloride (300 mL). The mixture wasstirred for 3 hours at room temperature after which it was poured into1N HCl (50 mL). The organic layer was washed with 1N HCl (2×50 mL), 1NNaOH (2×50 mL), dried (MgSO₄) and concentrated. The residue wastriturated with hexane to give a pale yellow solid (18.2 g, 59%), m.p.57.9-58.4; MS m/e 155.2 (M⁺ +H) NMR (CDCl₃ /TMS) d 0.96 (t, 3H, J=7 Hz,CH₃), 1.69 (m, 2H, CH₂), 1.70 (s, 6H, 2 CH₃), 2.18 (t, 2H, J=7 Hz, CH₂),5.74 (s, 1H, NH).

PART B: Preparation of 2-N-Butyramido-isobutylamide

2-N-Butyramido isobutyronitrile (6.0 g, 38.9 mmol) was dissolved inconcentrated hydrochloric acid (10 mL) at 0° C. Cold water (50 mL) wasadded immediately followed by treatment with concentrated ammoniumhydroxide to pH 5-6. The mixture was extracted successively withmethylene chloride. The organic layer was combined and concentrated togive white solid (5.4 g, 82%). M.P. 155.9-157.4, M.S. m/e 173.2 (M⁺ +H)NMR (CDCl₃ /TMS) d 0.95 (t, 3H, J=7Hz, CH₃), 1.59 (s, 6H, 2 CH₃), 1.66(m, 2H, CH₂), 2.17 (t, 2H, J=7 Hz, CH₂), 5.57 (s, 1H, NH), 6.10 (s, 1H,NH), 6.60 (s, 1H, NH).

PART C: Preparation of 2-Propyl-4,4-dimethyl-1H-imidazol-5(4H)-one

2-N-Butyramido-isobutylamide (5.4 g, 31.4 mmol) was dissolved in 1Nsodium hydroxide (40 mL) and heated at 80° C. for 30 minutes. Themixture was cooled to room temperature and extracted successively withethyl acetate. The combined organic layer was concentrated and theresidue was chromatographed over silica gel eluting with ethyl acetateto give 2.1 g white solid: m.p. 66.5-68.5 M.S. m/e 155.2 (M⁺ +H) NMR(CDCl₃ /TMS) d 1.01 (t, 3H, J=7 Hz, CH₃), 1.34 (s, 6H, 2 CH₃), 1.73 (m,2H, CH₂), 2.44 (t, 2H, J=7 Hz, CH₂).

PART D: Preparation of1,5-Dihydro-5,5-dimethyl-2-propyl-1-[(2'-(triphenyl methyltetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

A mixture of potassium carbonate (500 mg, 3.7 mmol),2-propyl-4-4-dimethyl-1H-imidazol-5(4H)-one (0.6 g, 3.9 mmol), and4'-bromomethyl-2-(triphenyl methyl tetrazol-5-yl)biphenyl (1.08 g, 1.9mmol) in dimethyl formamide (5 mL) was allowed to stir at roomtemperature overnight. The mixture was chromatographed over silica geleluting with ethyl acetate-hexane to give1,5-dihydro-5,5-dimethyl-2-propyl-1-[(2'-(triphenyl methyltetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one (70 mg, 14%) M.S. m/e 631.5 (M⁺ +H) NMR (CDCl₃ /TMS) δ0.88 (t, 3H, J=7 Hz, CH₃),1.38 (s, 6H, 2 CH₃), 1.67 (m, 2H, CH₂), 2.21 (t, 2H, J=7Hz, CH₂), 4.56(s, 2H, CH₂), 6.92 (d, J= 7 Hz, 8H, H_(arom)), 7.11 (d, J=7 Hz, 2H,H_(arom)), 7.24-7.38 (m, 10H, H_(arom)), 7.47 (m, 2H, H_(arom)), 7.92(m, 1H, H_(arom)).

PART E: Preparation of1,5-Dihydro-5,5-dimethyl-2-propyl-1-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

1,5-Dihydro-5,5-dimethyl-2-propyl-1-[(2'-(triphenyl methyltetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one (60 mg, 0.1mmol) in tetrahyrofuran (5 mL) and 10% hydrochloric acid (3 mL) wasallowed to stir at room temperature overnight. The reaction mixture wastreated with 50% sodium hydroxide to pH 8, concentrated and cooled inice bath. The precipitate was filtered and the aqueous solution wasadjusted to pH 3 using concentrated hydrochloric acid to give whitesolid which was recrystalized from ethyl acetate hexane to giveamorphous solid (23 mg, 62%). M.P. 127.5-129.9 M.S. m/e 389.2 (M⁺ +H)NMR (CDCl₃ /TMS) δ0.98 (t, 3H, J=7 Hz, CH₃), 1.50 (s, 6H, 2 CH₃), 1.76(m, 2H, CH₂), 2.64 (t, 2H, J=7 Hz, CH₂), 4.77 (s, 2H, CH₂), 7.14 (s 4H,H_(arom)), 7.41-7.58 (m, 3H, H_(arom)), 7.90 (m, 1H, H_(arom)).

EXAMPLE 2 3,5-Dihydro-5-(1-phenylethylidene)-2-propyl-3-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

PART A: Preparation of2-propyl-4-(1-phenylethyledene)-1H-imidazol-5(4H)-one

To a mixture of acetophenone (1.2 mL, 0.01 mol), glycine ethyl esterhydrochloride (2.80 g, 0.02 mol) and ethyl butyrimidate (3.0 g, 0.02mol) in 100 mL toluene was added triethyl amine (7.0 mL, 5 eq.). Themixture was heated at 80° C. under N₂ for 12 hours. The solvent wasremoved and the residue was partitioned between CH₂ Cl₂ and water. Thelayers were separated. The aqueous layer was extracted with CH₂ Cl₂. Thecombined organic layer was washed with brine, concentrated andchromatographed over silica gel eluting with 1:1 hexane:ethyl acetate,to give 0.35 g of the z isomer and 0.08 g of the E isomer. M.S. m/e 229(M⁺ +H) Z isomer, NMR (CDCl₃ /TMS) δ1.01 (t, 3H, CH₃), 1.76 (m, 2H,CH₂), 2.53 (t, 2H, CH₂), 2.73 (s, 3H, CH₃), 7.39 (m, 3H, H_(arom)), 7.78(d, 2H, H_(arom)), 9.30 (S, 1H, NH). E isomer, NMR (CDCl₃ /TMS) δ1.01(t, 3H, CH₃), 1.72 (m, 2H, CH₂), 2.48 (t, 2H, CH₂), 2.50 (s, 3H, CH₃),7.40 (m, 5H, H_(arom)), 9.00 (S, 1H, NH).

PART B: Preparation of3,5-dihydro-5-(1-phenylethylidene)-2-propyl-3-[(2'-(triphenylmethyltetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

Sodium hydride (0.15 g, 1.5 eq., 50% suspention in oil) was added to0.2-propyl-4-(1-phenylethyledene)-1H-imidazol-5(4H)-one (0.47 g, 2.1mmol) in dimethyl formamide (20 mL). The mixture was allowed to stir atroom temperature for 15 minutes. 4'-Bromomethyl-2(triphenyl methyltetrazol-5-yl) biphenyl (1.50 g, 1.28 eq.) was added and the reactionmixture was allowed to stir at room temperature overnight. The reactionmixture was poured into water and extracted with ether. The organiclayer was washed successively with water and saturated sodium chloridesolution, dried (MgSO₄) and concentrated. The residue waschromatographed over silica gel eluting with ethyl acetate-hexane 1:4 togive 3,5-dihydro-5-(1-phenylethyledene)-2-propyl-3-[(2'-(triphenylmethyl tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one(0.22 g, light yellow foam). NMR (CDCl₃ /TMS) δ0.89 (t, 3H, CH₃), 1.60(m, 2H, CH₂), 2.31 (m, 2H, CH₂), 2.80 (s, 3H, CH₃), 4.70 (s, 2H, CH₂),6.91 (d, 6H, H_(arom)), 6.99 (d, 2H, H_(arom)), 7.10 (d, 2H, H_(arom)),7.20-7.50 (m, 15H, H_(arom)), 7.80 (d, 2H, H_(arom)), 7.92 (d, 1H,H_(arom)).

PART C: Preparation of3,5-dihydro-5-(1-phenylethylidene)-2-propyl-3-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

3,5-dihydro-5-(1-phenylethylidene)-2-propyl-3-[(2'-(triphenylmethyltetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one(0.17 g) in tetrahydrofuran (20 mL) and 10% hydrochloric acid (5 mL) wasallowed to stir at room temperature for 3.5 hr. The reaction mixture wastreated with 50% sodium hydroxide to pH 8, concentrated and cooled inice bath. The precipitate was filtered and the aqueous solution wasadjusted to pH 4-5 using concentrated hydrochloric acid to give whitesolid which was washed with cold water and dried to give yellow solid(80 mg) as a mixture of the Z and E isomers (8:2). M.S. m/e 463 (M⁺ +H)NMR (CDCl₃ /TMS) δ0.98 (t, 3H, CH₃), 1.67 (m, 2H, CH₂), 2.39 (t, 2H,CH₂), 2.76 (s, 3H, CH₃), 4.80 (s, 2H, CH₂), 7.04-7.20 (m, 4H, H_(arom)),7.42-7.61 (m, 2H, H_(arom)), 7.63 (d, 2H, H_(arom)), 7.99 (d, 1H,H_(arom)).

EXAMPLE 33,5-Dihydro-5-(diphenylmethylene)-2-propyl-3-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one

A mixture of potassium carbonate (83 mg, 2 eq.),2-propyl-4-(diphenylmethylene)-1H-imidazol-5(4H)-one (90 mg, 0.3 mmol),and 4'-bromomethyl-2-(triphenyl methyl tetrazol-5-yl)biphenyl (0.21 g,1.2 eq.) in dimethyl formamide (10 mL) was allowed to stir at roomtemperature for 2 days. The solvent was in vacuo, the residue wasdissolved in CH₂ Cl₂ and washed with water and brine. The organic layerwas dried over MgSO₄ and concentrated. The crude mixture waschromatographed over silica gel eluting with ethyl acetate-hexane (1:4)to give 3,5-dihydro-5-(diphenylmethylene)-2-propyl-3-[(2'-(triphenylmethyl tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-one (100mg). M.S. m/e 767 (M⁺ +H) NMR (CDCl₃ /TMS) δ0.90 (m, 3H, CH₃), 1.65 (m,2H, CH₂), 2.38 (m, 2H, CH₂), 4.62 (s, 2H, CH₂), 6.88-7.50 (m, 30H,H_(arom)), 7.61 (m, 2H, H_(arom)), 7.90 (d, 1H, H_(arom)). The abovecompound was detritylated following the procedure described in Example2C, to give 61 mg of the desired product. M.S. m/e 524 (M⁺ +H) NMR(CDCl₃ /TMS) d 1.01 (t, 3H, CH₃), 1.78 (m, 2H, CH₂), 2.49 (t, 2H, CH₂),4.75 (s, 2H, CH₂), 7.12-7.41 (m, 15H, H_(arom)), 7.58 (m,2H, H_(arom)),8.10 (d, 1H, H_(arom)).

Compounds 1-325 in Table 1 can be prepared by the procedures describedin Examples 1, 2, 3 employing the appropriately substitutedimidazolinones and benzyl halides.

                                      TABLE 1                                     __________________________________________________________________________     ##STR27##                                                                                                                              M.S.                                                                          (M.sup.+  +         Ex.                                                                              R.sup.6    R.sup.7                                                                              R.sup.8     R.sup.9                                                                              R.sup.10                                                                           R.sup.14     H)                  __________________________________________________________________________    1  n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           1H-Tetrazol-5-yl                                                                           389                 2  n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O           1H-Tetrazol-5-yl                                                                           463                 3  n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O           1H-Tetrazol-5-yl                                                                           525                 4  n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           CONHSO.sub.2 C.sub.6                                                          H.sub.5                          5  n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOC.sub.6                                                          H.sub.5                          6  n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                        7  n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5)                         8  n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2                                                         C.sub.6 H.sub.5                  9  n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           CO.sub.2 H                       10 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           CH.sub.2 CO.sub.2 H              11 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           C(CF.sub.3).sub.2 OH             12 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           CONHNHSO.sub.2 CF.sub.3          13 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOC.sub.6                                                          H.sub.5                                                                       (R.sup.2 = CH.sub.3)             14 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = CH.sub.3)             15 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5)                                                                      (R.sup.2 = CH.sub.3)             16 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           CONHOCH.sub.3 (R.sup.2 =                                                      CH.sub.3)                        17 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-Bu)                                                           (R.sup.2 = CH.sub.3)             18 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2                                                         C.sub.6 H.sub.5                                                               (R.sup.2 = CH.sub.3)             19 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONH(n-Bu)                                                         (R.sup.2 = CH.sub.3)             20 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = CH.sub.3)             21 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(i-C.sub.4                                                       H.sub.9)                                                                      (R.sup.2 = CH.sub.3)             22 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           CONHSO.sub.2 C.sub.2 H.sub.4                                                  OH                                                                            (R.sup.2 = CH.sub.3)             23 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           CONHSO.sub.2 NH(4-ClC.sub.6                                                   H.sub.4)                                                                      (R.sup.2 = CH.sub.3)             24 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           C(OH)CH.sub.3 PO.sub.3                                                        H.sub.2                          25 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOC.sub.6 H.sub.5                                                  (R.sup.2 = Cl)                   26 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub. 2 NHCO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = Cl)                   27 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5)                                                                      (R.sup.2 = Cl)                   28 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(i-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = Cl)                   29 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-Bu) (R.sup.2                                                  = Cl)                            30 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2                                                         C.sub.6 H.sub.5                                                               (R.sup.2 = Cl)                   31 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONH(n-Bu)                                                         (R.sup.2 = Cl)                   32 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHCOCF.sub.3 (R.sup.2 = Cl)      33 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHPO.sub.2 H (R.sup.2 = Cl)      34 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHCONHSO.sub.2 (i-C.sub.5                                                     H.sub.11)                                                                     (R.sup.2 = Cl)                   35 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 (cy-C.sub.3                                                        H.sub.5) (R.sup.2 = Cl)          36 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           OPO.sub.3 H.sub.2 (R.sup.2 =                                                  Cl)                              37 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOC.sub.6 H.sub.5                                                  (R.sup.2 = F)                    38 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = F)                    39 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5)                                                                      (R.sup.2 = F)                    40 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(i-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = F)                    41 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-Bu) (R.sup.2                                                  = F)                             42 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2                                                         C.sub.6 H.sub.5                                                               (R.sup.2 = F)                    43 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONH(n-Bu)                                                         (R.sup.2 = F)                    44 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           OSO.sub.3 H (R.sup.2 = F)        45 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           PO(OH)(n-C.sub.5 H.sub.11)                                                    (R.sup.2 = F)                    46 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           PO.sub.3 H.sub.2 (R.sup.2 =                                                   F)                               47 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.3 H (R.sup.2 = F)         48 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NH(4-C.sub.5                                                         NH.sub.4) (R.sup.2 = F)          49 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOC.sub.6 H.sub.5                                                  (R.sup.3 = n-Pr)                 50 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.3 = n-Pr)                 51 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5)                                                                      (R.sup.3 = n-Pr)                 52 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(i-C.sub.5                                                       H.sub.11)                                                                     (R.sup.3 = n-Pr)                 53 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-Bu) (R.sup.3                                                  = n-Pr)                          54 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2                                                         C.sub.6 H.sub.5                                                               (R.sup.3 = n-Pr)                 55 n-Pr       O                  CH.sub. 3                                                                            CH.sub.3                                                                           SO.sub.2 NHCONH(n-Bu)                                                         (R.sup.3 = n-Pr)                 56 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NH(n-Bu) (R.sup.3 =                                                  n-Pr)                            57 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONH(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                 58 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONH(i-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                 59 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONH(cy-C.sub.3                                                    H.sub.5)                                                                      (R.sup.3 = n-Pr)                 60 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONHCH.sub.2                                                       C.sub.6 H.sub.5                                                               (R.sup.3 = n-Pr)                 61 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOC.sub.6                                                          H.sub.5                                                                       (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            62 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            63 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub. 3                                                     H.sub.5)                                                                      (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            64 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(i-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            65 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-Bu)                                                           (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            66 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2                                                         C.sub.6 H.sub.5                                                               (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            67 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            68 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.4                                                     H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            69 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(i-C.sub.5                                                     H.sub.11)                                                                     (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            70 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(cy-C.sub. 3                                                   H.sub.5)                                                                      (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            71 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCOCH.sub.2                                                       C.sub.6 H.sub.5                                                               (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            72 n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCF.sub.3            73 n-Pr       N                  CH.sub.3                                                                             CH.sub.3                                                                           1H-Tetrazol-5-yl                 74 n-Pr       N                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(4Cl-C.sub.6                                                     H.sub.4)                         75 n-Pr       N                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = CH.sub.3)             76 n-Pr       N                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                 77 n-Pr       S                  CH.sub.3                                                                             CH.sub.3                                                                           1H-Tetrazol-5-yl                 78 n-Pr       S                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(4Cl-C.sub.6                                                     H.sub.4)                         79 n-Pr       S                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = CH.sub.3)             80 n-Pr       S                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 =  n-Pr)                81 n-Bu       N                  CH.sub.3                                                                             CH.sub.3                                                                           1H-Tetrazol-5-yl                 82 n-Bu       S                  CH.sub.3                                                                             CH.sub.3                                                                           1H-Tetrazol-5-yl                 83 n-Bu       S                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)            84 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           CONHSO.sub.2 C.sub.6                                                          H.sub.5                          85 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOC.sub.6                                                          H.sub.5                          86 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                        87 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5)                         88 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2 Ph         89 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(i-C.sub.4                                                     H.sub.9)                         90 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)            91 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                        92 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(cy-C.sub.3                                                    H.sub.5)                         93 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCOCH.sub.2 Ph       94 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(4ClC.sub.6                                                      H.sub.4)                         95 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.3 = n-Pr)                 96 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = CH.sub.3)             97 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                 98 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = Cl)                   99 n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCF.sub.3            100                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            101                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(i-C.sub.5                                                     H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            102                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONH(n-Bu)                                                         (R.sup.2 = Cl)                   103                                                                              n-Pr       S                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)            104                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           CONHSO.sub.2 C.sub.6                                                          H.sub.5                          105                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOC.sub.6 H.sub.                                                   5                                106                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                        107                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5)                         108                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2 Ph         109                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(i-C.sub.4                                                     H.sub.9)                         110                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)            111                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                        112                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(cy-C.sub.3                                                    H.sub.5)                         113                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCOCH.sub.2 Ph       114                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(4ClC.sub.6                                                      H.sub.4)                         115                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.3 = n-Pr)                 116                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = CH.sub.3)             117                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                 118                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = Cl)                   119                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOCF.sub.3            120                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            121                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(i-C.sub.5                                                     H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            122                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCONH(n-Bu)                                                         (R.sup.2 = Cl)                   123                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    1H-Tetrazol-5-yl                 124                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    CONHSO.sub.2 C.sub.6                                                          H.sub.5                          125                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    SO.sub.2 NHCOC.sub.6                                                          H.sub.5                          126                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    SO.sub.2 NHCO(n-C.sub.5                                                       H.sub. 11)                       127                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5)                         128                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    SO.sub.2 NHCOCH.sub.2 Ph         129                                                                              n-Bu       O                  CF.sub.3                                                                             CF.sub.3                                                                           NHSO.sub.2 NHCO(i-C.sub.4                                                     H.sub.9)                         130                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    NHSO.sub.2 NHCO(n-Bu)            131                                                                              n-Pr       O                  CF.sub.3                                                                             CF.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                        132                                                                              n-Pr       O                  CF.sub.3                                                                             CF.sub.3                                                                           NHSO.sub.2 NHCO(cy-C.sub.3                                                    H.sub.5)                         133                                                                              n-Bu       O                  CF.sub.3                                                                             CF.sub.3                                                                           NHSO.sub.2 NHCOCH.sub.2 Ph       134                                                                              n-Bu       O                  CF.sub.3                                                                             CF.sub.3                                                                           SO.sub.2 NHCO(4ClC.sub.6                                                      H.sub.4)                         135                                                                              pFPh       O                  CF.sub.3                                                                             CF.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.3 = n-Pr)                 136                                                                              pFPh       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = CH.sub.3)             137                                                                              pFPh       O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                 138                                                                              Ph         O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = Cl)                   139                                                                              Ph         O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOCF.sub.3            140                                                                              Ph         O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            141                                                                              CH.sub.3   O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(i-C.sub.5                                                     H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            142                                                                              CH.sub.3   O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCONH(n-Bu)                                                         (R.sup.2 = Cl)                   143                                                                              CH.sub.3   O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)            144                                                                              CH.sub.3   O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    CONHSO.sub.2 C.sub.6                                                          H.sub.5                          145                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    SO.sub.2 NHCOC.sub.6                                                          H.sub.5                          146                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                        147                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(cy-C.sub.3                                                      H.sub.5 )                        148                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOCH.sub.2 Ph         149                                                                              CH.sub.3 CH.sub.2 CHCH.sub.2                                                             O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(i-C.sub.4                                                     H.sub.9)                         150                                                                              CH.sub.3 CH.sub.2 CHCH.sub.2                                                             O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-gu)            151                                                                              CH.sub.3 CH.sub.2 CHCH.sub.2                                                             O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                        152                                                                              CH.sub.3 CH.sub.2 CHCH.sub.2                                                             O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCO(cy-C.sub.3                                                    H.sub.5)                         153                                                                              C.sub.2 H.sub.5                                                                          O                  CH.sub.3                                                                             CH.sub.3                                                                           NHSO.sub.2 NHCOCH.sub.2 Ph       154                                                                              C.sub.2 H.sub.5                                                                          O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCO(4ClC.sub.6                                                      H.sub.4)                         155                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.3 = n-Pr)                 156                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = CH.sub.3)             157                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                 158                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = Cl)                   159                                                                              n-Pr       O                  (CH.sub.2).sub.5                                                                          SO.sub.2 NHCOCF.sub.3            160                                                                              n-Pr       O                  (CH.sub.2).sub.4                                                                          SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = Cl, R.sup.3 =                                                      n-Pr)                            161                                                                              n-Pr       O                  (CH.sub.2).sub.2                                                                          NHSO.sub.2 NHCO(i-C.sub.5                                                     H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-Pr)                            162                                                                              n-Pr       O                  cy-Pr  cy-Pr                                                                              NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = CH.sub.3)             163                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  S      1H-Tetrazol-5-yl                      164                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      CONHSO.sub.2 C.sub.6 H.sub.5          165                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      SO.sub.2 NHCOC.sub.6 H.sub.5          166                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             N                                     167                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      SO.sub.2 NHCO(cy-C.sub.3 H.sub.5)                                             O                                     168                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      SO.sub.2 NHCOCH.sub.2 Ph              169                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      NHSO.sub.2 NHCO(i-C.sub.4                                                     H.sub.9)                              170                                                                              n-Bu       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      NHSO.sub.2 NHCO(n-Bu)                 171                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                             172                                                                              C.sub.2 H.sub.3                                                                          C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      NHSO.sub.2 NHCO(cy-C.sub.3                                                    H.sub.5)                              173                                                                              n-Bu       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      NHSO.sub.2 NHCOCH.sub.2 Ph            174                                                                              Ph         C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      SO.sub.2 NHCO(4ClC.sub.6 H.sub.4)     175                                                                              pFPh       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             (R.sup.3 = n-Pr)                      176                                                                              n-Pr       C(C.sub.6 H.sub.5 )                                                                  (CH.sub.3)  O      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             (R.sup.2 = CH.sub.3)                  177                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                      178                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O      NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = Cl)                        179                                                                              n-Pr       CH.sub.3                                                                             CH.sub.3    N      SO.sub.2 NHCOCF.sub.3                 180                                                                              CH.sub.3   CH.sub.3                                                                             CH.sub.3    N      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             N                                                                             (R.sup.2 = Cl, R.sup.3 = n-Pr)        181                                                                              Ph         CH.sub.3                                                                             CH.sub.3    N      NHSO.sub.2 NHCO(i-C.sub.5                                                     H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 = n-Pr)         182                                                                              pFPh       CH.sub.3                                                                             CH.sub.3    N      SO.sub.2 NHCONH(n-Bu)                                                         (R.sup.2 = Cl)                        183                                                                              n-Pr       C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                           N      1H-Tetrazol-5-yl                      184                                                                              n-Pr       C.sub.2 H.sub.5                                                                      CH.sub.3    N      SO.sub.2 NHCO(4ClC.sub. 6                                                     H.sub.4)                              185                                                                              n-Pr       CF.sub.3                                                                             CF.sub.3    N      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             N                                                                             (R.sup.2 = CH.sub.3)                  186                                                                              n-Bu       CH.sub.3                                                                             CH.sub.3    N      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                      187                                                                              n-Pr       CH.sub.3                                                                             CH.sub.3    N      1H-Tetrazol-5-yl                      188                                                                              n-Pr       CF.sub.3                                                                             CF.sub.3    N      SO.sub.2 NHCO(4ClC.sub.6 H.sub.4)                                             O                                     189                                                                              n-Pr       (CH.sub.2).sub.2   N      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             O                                                                             (R.sup.2 = CH.sub.3)                  190                                                                              n-Pr       (CH.sub.2).sub.2   N      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                             191                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         S      1H-Tetrazol-5-yl                      192                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         S      1H-Tetrazol-5-yl                      193                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         N      1H-Tetrazol-5-yl                      194                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      CONHSO.sub.2 C.sub.6 H.sub.5          195                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      SO.sub.2 NHCOC.sub.6 H.sub.5          196                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)     197                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      SO.sub.2 NHCO(cy-C.sub.3 H.sub.5)     198                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      SO.sub.2 NHCOCH.sub.2 Ph              199                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      NHSO.sub.2 NHCO(i-C.sub.4                                                     H.sub.9)                              200                                                                              n-Bu       C(C.sub.6 H.sub.5).sub.2                                                                         O      NHSO.sub.2 NHCO(n-Bu)                 201                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                             202                                                                              C.sub.2 H.sub.3                                                                          C(C.sub.6 H.sub.5).sub.2                                                                         O      NHSO.sub.2 NHCO(cy-C.sub.3                                                    H.sub.5)                              203                                                                              Ph         C(C.sub.6 H.sub.5).sub.2                                                                         O      SO.sub.2 NHCO(4ClC.sub.6 H.sub.4)     204                                                                              pFPh       C(C.sub.6 H.sub.5).sub.2                                                                         O      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             (R.sup.3 = n-Pr)                      205                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = CH.sub.3)                  206                                                                              n-Pr       C(C.sub.6 H.sub. 5).sub.2                                                                        O      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             (R.sup.2 = CH.sub.3)                  207                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                      208                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                             (CH.sub.3)  O      NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = Cl)                        209                                                                              n-Bu       (CH.sub.2).sub.3.sup.-                                                                           N      NHSO.sub.2 NHCOCH.sub.2 Ph            210                                                                              Ph         (CH.sub.2).sub.4.sup.-                                                                           N      SO.sub.2 NHCO(4ClC.sub.6 H.sub.4)                                             N                                     211                                                                              pFPh       (CH.sub.2).sub.4.sup.-                                                                           N      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             O                                                                             (R.sup.3 = n-Pr)                      212                                                                              n-Pr       (CH.sub.2).sub.4.sup.-                                                                           N      NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = CH.sub.3)                  213                                                                              n-Pr       (CH.sub.2).sub.5.sup.-                                                                           N      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             (R.sup.2 = CH.sub.3)                  214                                                                              n-Pr       (CH.sub.2).sub.5   N      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11 )                                                                    (R.sup.3 = n-Pr)                      215                                                                              n-Bu       (CH.sub.2).sub.4   N      NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = CH.sub.3)                  216                                                                              n-Pr       CH.sub.3                                                                              ##STR28##  O      1H-Tetrazol-5-yl                      217                                                                              n-Pr       CH.sub.3                                                                              ##STR29##  O      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             R.sup.2 = CH.sub.3)                   218                                                                              n-Pr       H                                                                                     ##STR30##  O      1H-Tetrazol-5-yl                      219                                                                              n-Pr       H                                                                                     ##STR31##  O      SO.sub.2 NHCO(n-C.sub.5 H.sub.11)                                             R.sup.2 = CH.sub.3)                   220                                                                              n-Pr       H      CH.sub.2 COOH                                                                             O      1H-Tetrazol-5-yl                      221                                                                              n-Pr       H      CH.sub.2 COOH                                                                             O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11)                                                                     (R.sup.3 = n-Pr)                      222                                                                              n-Pr       H      CH.sub.2 COOH                                                                             O      SO.sub.2 NHCO(cy-C.sub.3 H.sub.5)     223                                                                              n-Pr       H      CH.sub.2 COOH                                                                             O      NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = CH.sub.3)                  224                                                                              n-Pr       CH.sub.3                                                                             CH.sub.2 COOH                                                                             O      NHSO.sub.2 NHCO(n-Bu)                                                         (R.sup.2 = CH.sub.3)                  225                                                                              n-Pr       H                                                                                     ##STR32##  O      1H-Tetrazol-5-yl                      226                                                                              n-Pr       CH.sub.3                                                                              ##STR33##  O      1H-Tetrazol-5-yl                      227                                                                              n-Pr       H                                                                                     ##STR34##  O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11) (R.sup.2 = CH.sub.3)        228                                                                              n-Pr       CH.sub.3                                                                              ##STR35##  O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11) (R.sup.2 = CH.sub.3)        229                                                                              n-Pr       H                                                                                     ##STR36##  O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11) (R.sup.3 = n-Pr)            230                                                                              n-Pr       CH.sub.3                                                                              ##STR37##  O      NHSO.sub.2 NHCO(n-C.sub.5                                                     H.sub.11) (R.sup.3 = n-Pr)            231                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOO(i-C.sub.4 H.sub.9)                                             N                                     232                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOO(n-C.sub.4 H.sub.9)                                             O                                     233                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOO(n-C.sub.5 H.sub.11)    234                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOO(i-C.sub.5 H.sub.11)    235                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOO(n-C.sub.5 H.sub.11)                                     (R.sup.2 = CH.sub.3)                         236                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOO(n-C.sub.4 H.sub.0)                                             N                                                                      (R.sup.2 = CH.sub.3)                         237                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOO(i-C.sub.5 H.sub.11)                                            O                                                                      (R.sup.2 = CH.sub.3 )                        238                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                                                               (R.sup.2 = CH.sub.3)                         239                                                                              n-Pr       O      CH.sub.3    CH.sub.3                                                                             SO.sub.2 NHCOOCH.sub.2 C.sub.6                                                H.sub.5                                                                (R.sup.2 = CH.sub.3)                         240                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = Cl)                   241                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = Cl)                   242                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = Cl)                   243                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                                                                      (R.sup.2 = Cl)                   244                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOOCH.sub.2                                                        C.sub.6 H.sub.5                                                               (R.sup.2 = Cl)                   245                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = F)                    246                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = F)                    247                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = F)                    247                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                                                                      (R.sup.2 = F)                    248                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOOCH.sub.2                                                        C.sub.6 H.sub.5                                                               (R.sup.2 = F, R.sup.3 =                                                       n-C.sub.3 H.sub.7)               249                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         250                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         251                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         252                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                                                                      (R.sup.3 =  n-C.sub.3                                                         H.sub.7)                         253                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOOCH.sub.2                                                        C.sub.6 H.sub.5                                                               (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         254                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = Cl, R.sup.3 =                                                      n-C.sub.3 H.sub.7)               255                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-C.sub.3 H.sub.7)               256                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = Cl, R.sup.3 =                                                      n-C.sub.3 H.sub.7)               257                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                                                                      (R.sup.2 = Cl, R.sup.3 =                                                      n-C.sub.3 H.sub.7)               258                                                                              n-Pr       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOOCH.sub.2                                                        C.sub.6 H.sub.5                                                               (R.sup.2 = F, R.sup.3 =                                                       n-C.sub.3 H.sub.7)               259                                                                              n-Pr       N                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         260                                                                              n-Pr       S                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         261                                                                              n-Bu       S                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         262                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.4                                                      H.sub.9)                         263                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         264                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                        265                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                         266                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOOCH.sub.2 Ph                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         267                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         268                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9 )                                                                     (R.sup.2 = Cl)                   269                                                                              n-Bu       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-C.sub.3 H.sub.7)               270                                                                              n-Pr       S                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         271                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.4                                                      H.sub.9)                         272                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         273                                                                              n-Pr       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                        274                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                         275                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOOCH.sub.2 Ph        276                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         277                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = Cl)                   278                                                                              n-Bu       O                  C.sub.2 H.sub. 5                                                                     CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-C.sub.3 H.sub.7)               279                                                                              n-Bu       O                  CF.sub.3                                                                             CF.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.4                                                      H.sub.9)                         280                                                                              n-Bu       O                  C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                    SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         281                                                                              n-Pr       O                  CF.sub.3                                                                             CF.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                        282                                                                              n-Pr       O                  CF.sub.3                                                                             CF.sub.3                                                                           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                         283                                                                              n-Bu       O                  CF.sub.3                                                                             CF.sub.3                                                                           SO.sub.2 NHCOOCH.sub.2 Ph        284                                                                              pFPh       O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         285                                                                              Ph         O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = Cl)                   286                                                                              CH.sub.3   O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-C.sub.3 H.sub.7)               287                                                                              CH.sub.3   O                  C.sub.2 H.sub.5                                                                      CH.sub. 3                                                                          SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         288                                                                              CH.sub.3 CH.sub.2 CHCH.sub.2                                                             O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(i-C.sub.4                                                      H.sub.9)                         289                                                                              CH.sub.3 CH.sub.2 CHCH.sub.2                                                             O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         290                                                                              CH.sub.3 CH.sub.2 CHCH.sub.2                                                             O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                        291                                                                              CH.sub.3 CH.sub.2 CHCH.sub.2                                                             O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                         292                                                                              C.sub.2 H.sub.5                                                                          O                  CH.sub.3                                                                             CH.sub.3                                                                           SO.sub.2 NHCOOCH.sub.2 Ph        293                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         294                                                                              C.sub.2 H.sub.5                                                                          O                  C.sub.2 H.sub.5                                                                      CH.sub.3                                                                           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = Cl)                   295                                                                              n-Pr       O                  (CH.sub.2).sub.2                                                                          SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-C.sub. 3 H.sub.7)              296                                                                              n-Pr       O                  cy-Pr  cy-Pr                                                                              SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = CH.sub.3)             297                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O           SO.sub.2 NHCOO(i-C.sub.4                                                      H.sub.9)                         298                                                                              n-Bu       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         299                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                        300                                                                              C.sub.2 H.sub.3                                                                          C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                         301                                                                              n-Bu       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O           SO.sub.2 NHCOOCH.sub.2 Ph        302                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         303                                                                              n-Pr       C(C.sub.6 H.sub.5)                                                                   (CH.sub.3)  O           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = Cl)                   304                                                                              Ph         CH.sub.3                                                                             CH.sub.3    N           SO.sub.2 NHCOO(i-C.sub.5                                                      H.sub.11)                                                                     (R.sup.2 = F, R.sup.3 =                                                       n-C.sub.3 H.sub.7)               305                                                                              n-Bu       CH.sub.3                                                                             CH.sub.3    N           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         306                                                                              n-Pr       (CH.sub.2).sub.2   N           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                        307                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O           SO.sub.2 NHCOO(i-C.sub.4                                                      H.sub.9)                         308                                                                              n-Bu       C(C.sub.6 H.sub.5).sub.2                                                                         O           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                         309                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O           SO.sub.2 NHCOO (n-C.sub.5                                                     H.sub.11)                        310                                                                              C.sub.2 H.sub.3                                                                          C(C.sub.6 H.sub.5).sub.2                                                                         O           SO.sub.2 NHCOO(cy-C.sub.3                                                     H.sub.5)                         311                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = CH.sub.3)             312                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O           SO.sub.2 NHCO(n-C.sub.5                                                       H.sub.11)                                                                     (R.sup.2 = CH.sub.3)             313                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                                         O           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         314                                                                              n-Pr       C(C.sub.6 H.sub.5).sub.2                                                             (CH.sub.3)  O           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = Cl)                   315                                                                              n-Bu       (CH.sub.2).sub.3   N           SO.sub.2 NHCOOCH.sub.2 Ph        316                                                                              n-Pr       (CH.sub.2).sub.4   N           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = CH.sub.3)             317                                                                              n-Pr       (CH.sub.2).sub.5   N           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         318                                                                              n-Bu       (CH.sub.2).sub.4   N           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = CH.sub.3)             319                                                                              n-Pr       H      CH.sub.2 COOH                                                                             O           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11)                                                                     (R.sup.3 = n-C.sub.3                                                          H.sub.7)                         320                                                                              n-Pr       H      CH.sub.2 COOH                                                                             O           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = CH.sub.3)             321                                                                              n-Pr       CH.sub.3                                                                             CH.sub.2 COOH                                                                             O           SO.sub.2 NHCOO(n-C.sub.4                                                      H.sub.9)                                                                      (R.sup.2 = CH.sub.3)             322                                                                              n-Pr       H                                                                                     ##STR38##  O           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11) (R.sup.2 =                                                          CH.sub.3)                        323                                                                              n-Pr       CH.sub.3                                                                              ##STR39##  O           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11) (R.sup.2 =                                                          CH.sub.3)                        324                                                                              n-Pr       H                                                                                     ##STR40##  O           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11) (R.sup.3 =                                                          n-C.sub.3 H.sub.7)               325                                                                              n-Pr       CH.sub.3                                                                              ##STR41##  O           SO.sub.2 NHCOO(n-C.sub.5                                                      H.sub.11) (R.sup.3 =                                                          n-C.sub.3 H.sub.7)               __________________________________________________________________________

Utility

Angiotensin II (AII) produces numerous biological responses (e.g.,vasoconstriction) through stimulation of its receptors on cellmembranes. For the purpose of identifying compounds such as AIIantagonists which are capable of interacting with the AII receptor, aligand-receptor binding assay was utilized for the initial screen. Theassay was carried out according to the method described by Chiu, et al.,Receptor, 1 33, (1990). In brief, aliquots of a freshly preparedparticulate fraction of rat adrenal cortex were incubated with 0.05 nM[¹²⁵ I] AII and varying concentrations of potential AII antagonists in aTris buffer. After a 1 h incubation the reaction was terminated byaddition of cold assay buffer. The bound and free radioactivity wererapidly separated through glass-fiber filters, and the trappedradioactivity was quantitated by scintillation counting. The inhibitoryconcentration (IC₅₀) of potential AII antagonists which gives 50%displacement of the total specifically bound [¹²⁵ I] AII is presented asa measure of the affinity of such compound for the AII receptor.

Using the assay method described above, the compounds of this inventionare found to exhibit an activity of at least IC₅₀ <10 micromolar,thereby demonstrating and confirming the activity of these compounds aseffective AII antagonists.

The potential antihypertensive effects of the compounds of thisinvention may be demonstrated by administering the compounds to awakerats made hypertensive by ligation of the left renal artery [Cangiano etat., J. Pharmacol. Exp. Ther., 1979, 208, 310]. This procedure increasesblood pressure by increasing renin-Production with consequent elevationof AII levels. Compounds are administered intravenously via a cannula inthe jugular vein at 10 mg/kg. Arterial blood pressure is continuouslymeasured directly through a carotid artery cannula and recorded using apressure transducer and a polygraph. Blood pressure levels aftertreatment are compared to pretreatment levels to determine theantihypertensive effects of the compounds.

Using the in vivo methodology described above, the compounds of thisinvention are found to exhibit an activity (intravenous) which is 10mg/kg or less, and/or an activity (oral) which is 100 mg/kg or less,thereby demonstrating and confirming the utility of these compounds aseffective agents in lowering blood pressure.

The compounds of the invention are useful in treating hypertension. Theyare also of value in the management of acute and chronic congestiveheart failure and angina. These compounds may also be expected to beuseful in the treatment of primary and secondary hyperaldosteronism;renal diseases such as diabetic nephropathy, glomerulonephritis,glomerular sclerosis, nephrotic syndrome, hypertensive nephrosclerosis,end stage renal disease, used in renal transplant therapy, and to treatrenovascular hypertension, scleroderma, left ventricular dysfunction,systolic and diastolic dysfunction, diabetic retinopathy and in themanagement of vascular disorders such as migrate, Raynaud's disease, andas prophylaxis to minimize the atherosclerotic process and neointimalhyperplasia following angioplasty or vascular injury and to retard theonset of type II diabetes. The application of the compounds of thisinvention for these and similar disorders will be apparent to thoseskilled in the art.

The compounds of this invention are also useful to treat elevatedintraocular pressure and to enhance retinal blood flow and can beadministered to patients in need of such treatment with typicalpharmaceutical formulations such as tablets, capsules, injectables andthe like as well as topical ocular formulations in the form ofsolutions, ointments, inserts, gels and the like. Pharmaceuticalformulations prepared to treat intraocular pressure would typicallycontain about 0.1% to 15% by weight, preferably 0.5% to 2% by weight, ofa compound of this invention. For this use, the compounds of thisinvention may also be used in combination with other medications for thetreatment of glaucoma including choline esterase inhibitors such asphysostigmine salicylate or demecarium bromide, parasympathomineticagents such as pilocarpine nitrate, β-adrenergic antagonists such astimolol maleate, adrenergic agonists such as epinephrine and carbonicanhydrase inhibitors such as MK-507.

In the management of hypertension and the clinical conditions notedabove, the compounds of this invention may be utilized with apharmaceutical carrier in compositions such as tablets, capsules orelixirs for oral administration, suppositories for rectaladministration, sterile solutions or suspensions for parenteral orintramuscular administration, and the like. The compounds of thisinvention can be administered to patients (animals and human) in need ofsuch treatment in dosages that will provide optimal pharmaceuticalefficacy. Although the dose will vary from patient to patient dependingupon the nature and severity of disease, the patients weight, specialdiet that is being followed by a patient, concurrent medication, andother factors which those skilled in the art will recognize, the dosagerange will generally be about 1 to 1000 mg per patient per day which canbe administered in single or multiple doses. Preferably, the dosagerange will be about 5 to 500 mg per patient per day; more preferablyabout 5 to 300 mg per patient per day.

The compounds of this invention can also be administered in combinationwith other antihypertensives and/or diuretics. For example, thecompounds of this invention can be given in combination with diureticssuch as hydrochlorothiazide, chlorothiazide, chlorthalidone,methylclothiazide, furosemide, ethacrynic acid, triamterene, amiloridespironolactone and atriopeptin; calcium channel blockers, such asdiltiazem, felodipine, nifedipine, amlodipine, nimodipine, isradipine,nitrendipine and verapamil; β-adrenergic antagonists such as timolol,atenolol, metoprolol, propanolol, nadolol and pindolol; angiotensinconverting enzyme inhibitors such as enalapril, lisinopril, captopril,ramipril, quinapril and zofenopril; renin inhibitors such as A-69729, FK906 and FK 744; a-adrenergic antagonists such as prazosin, doxazosin,and terazosin; sympatholytic agents such as methyldopa, clonidine andguanabenzi atriopeptidase inhibitors (alone or with ANP) such asUK-79300; serotonin antagonists such as ketanserin; A₂ -adrenosinereceptor agonists such as CGS 22492C; potassium channel agonists such aspinacidil and cromakalim; and various other antihypertensive drugsincluding reserpine, minoxidil, guanethidine, hydralazinc hydrochlorideand sodium nitroprusside as well as combinations of the above-nameddrugs. Combinations useful in the management of congestive heart failureinclude, in addition, compounds of this invention with cardiacstimulants such as dobutamine and xamoterol and phosphodiesteraseinhibitors including amrinone and milrinone.

Typically, the individual daily dosages for these combinations can rangefrom about one-fifth of the minimally recommended clinical dosages tothe maximum recommended levels for the entities when they are givensingly. To illustrate these combinations, one of the angiotensin IIantagonists of this invention effective clinically in the 5-500milligrams per day range can be effectively combined at levels at the1.0-500 milligrams per day range with the following compounds at theindicated per day dose range; hydrochlorothiazide (6-100 mg),chlorothiazide (125-500 mg), ethacrynic acid (5-200 mg), amiloride (5-20mg), furosemide (5-80 mg), propranolol (10-480 mg), timolol maleate(1-20 mg), methyldopa (125-2000 mg), felodipine (1-20 mg), nifedipine(5-120 mg), nitrendipine (5-60 mg), and diltiazem (30-540 mg). Inaddition, triple drug combinations of hydrochlorothiazide (5-100 mg)plus amiloride (5-20 mg) plus angiotensin II antagonists of thisinvention (1-500 mg) or hydrochlorothiazide (5-100 mg) plus timololmaleate (5-60 mg) plus an angiotensin II antagonists of this invention(1-500 mg) or hydrochlorothiazide (5-200 mg) and nifedipine (5-60 mg)plus an angiotensin II antagonist of this invention (1-500 mg) areeffective combinations to control blood pressure in hypertensivepatients. Naturally, these dose ranges can be adjusted on a unit basisas necessary to permit divided daily dosage and, as noted above, thedose will vary depending on the nature and severity of the disease,weight of patient, special diets and other factors.

The active ingredient can be administered orally in solid dosage forms,such as capsules, tablets, and powders, or in liquid dosage forms, suchas elixirs syrups, and suspensions. It can also be administeredparenterally, in sterile liquid dosage forms.

Gelatin capsules contain the active ingredient and powdered carriers,such as lactose, starch, cellulose derivatives, magnesium stearate,stearic acid, and the like. Similar diluents can be used to makecompressed tablets. Both tablets and capsules can be manufactured assustained release products to provide for continuous release ofmedication over a period of hours. Compressed tablets can be sugarcoated or film coated to mask any unpleasant taste and protect thetablet from the atmosphere, or enteric coated for selectivedisintegration in the gastrointestinal tract

Liquid dosage forms for oral administration can contain coloring andflavoring to increase patient acceptance.

In general, water, a suitable oil, saline, aqueous dextrose (glucose),and related sugar solutions and glycols such as propylene glycol orpolyethylene glycols are suitable carriers for parenteral solutions.Solutions for parenteral administration preferably contain a watersoluble salt of the active ingredient, suitable stabilizing agents, andif necessary, buffer substances. Antioxidizing agents such as sodiumbisulfite, sodium sulfite, or ascorbic acid, either alone or combined,are suitable stabilizing agents. Also used are citric acid and its saltsand sodium EDTA. In addition, parenteral solutions can containpreservatives, such as benzalkonium chloride, methyl- or propylparaben,and chlorobutanol.

Suitable pharmaceutical carriers are described in Remington'sPharmaceutical Sciences, A. Osol, a standard reference text in thisfield.

Useful pharmaceutical dosage forms for administration of the compoundsof this invention can be illustrated as follows:

Capsules

A large number of unit capsules are prepared by filling standardtwo-piece hard gelatin capsules each with 100 milligrams of powderedactive ingredient, 150 milligrams of lactose, 50 milligrams ofcellulose, and 6 milligrams magnesium stearate.

Soft Gelatin Capsules

A mixture of active ingredient in a digestible oil such as soybean oil,cottonseed oil or olive oil is prepared and injected by means of apositive displacement pump into gelatin to form soft gelatin capsulescontaining 100 milligrams of the active ingredient. The capsules arewashed and dried.

Tablets

A large number of tablets are prepared by conventional procedures sothat the dosage unit is 100 milligrams of active ingredient, 0.2milligrams of colloidal silicon dioxide, 5 milligrams of magnesiumstearate, 275 milligrams of microcrystalline cellulose, 11 milligrams ofstarch and 98.8 milligrams of lactose. Appropriate coatings may beapplied to increase palatability or delay absorption.

Injectable

A parenteral composition suitable for administration by injection isprepared by stirring 1.5% by weight of active ingredient in 10% byvolume propylene glycol. The solution is made to volume with water forinjection and sterilized.

Suspension

An aqueous suspension is prepared for oral administration so that each 5milliliters contain 100 milligrams of finely divided active ingredient,100 milligrams of sodium carboxymethyl cellulose, 5 milligrams of sodiumbenzoate, 1.0 grams of sorbitol solution, U.S.P., and 0.025 millilitersof vanillin.

The same dosage forms can generally be used when the compounds of thisinvention are administered stepwise in conjunction with anothertherapeutic agent. When the drugs are administered in physicalcombination, the dosage form and administration route should be selectedfor compatibility with both drugs.

What is claimed is:
 1. A compound of the formula: ##STR42## wherein R²is(a) H, (b) halo, (c) C₁ -C₄ alkyl, (d) C₁ -C₄ alkoxy, R³ is(a) H, (b)halo, (c) C₁ -C₄ alkyl, (d) C₁ -C₄ alkoxy, (e) C₁ -C₄ alkoxyalkyl; R⁶is(a) C₁ -C₇ alkyl, (b) C₃ -C₄ alkenyl, (c) C₃ -C₄ alkynyl, (d) phenyl,optionally substituted with 1-2 substituents selected from the group ofhalo, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, nitro, amino, hydroxy and benzyloxy;R⁷ and R⁸ taken together are CR¹¹ R¹² ; R¹¹ and R¹² are independently(a)H, (b) C₁ -C₆ alkyl, (c) phenyl, (d) benzyl, R¹⁴ is(a) --CO₂ H, (b)--CONHSO₂ R²⁴, (c) --NHCONHSO₂ R²⁴, (d) --NHSO₂ R²⁴, (e) --SO₂ NHR²³,(f) --SO₂ NHCONHR²³, ##STR43## (h) --NHSO₂ NHCOR²⁴, (i) --SO₂ NHCOR²⁴ ;R²³ is(a) H, (b) C₁ -C₅ alkyl, (c) aryl, (d) --CH₂ -aryl, wherein arylis phenyl optionally substituted with 1-2 substituents selected from thegroup of halo, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, nitro, amino, hydroxy andbenzyloxy; R²⁴ is(a) aryl, where aryl is as defined above, (b) C₃ -C₇cycloalkyl, (c) C₁ -C₄ perfluoroalkyl, (d) C₁ -C₄ alkyl optionallysubstituted with a substituent selected from the group consisting ofaryl as defined above, --OH, --SH, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₁ -C₄alkylthio, --CF₃, halo, --NO₂, --CO₂ H, --CO₂ CH₃, --CO₂ --benzyl,--NH₂, C₁ -C₄ alkylamino, C₁ -C₄ dialkylamino, or --PO₃ H₂, (e) C₁ -C₄alkoxy optionally substituted with a substituent selected from the groupconsisting of aryl as defined above, --OH, --SH, C₁ -C₄ alkyl, C₁ -C₄alkoxy, C₁ -C₄ alkylthio, --CF₃, halo, --NO₂, --CO₂ H, --CO₂ CH₃, --CO₂-benzyl, --NH₂, C₁ -C₄ alkylamino, C₁ -C₄ dialkylamino, --PO₃ H₂ ; orapharmaceutically acceptable salt thereof.
 2. A compound of claim 1selected from the group consisting of3. 3.5-Dihydro-5-(1-phenylethylidene)-2-propyl-3-[(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]-4H-imidazol-4-oneand4'(3,5-dihydro-5-(1-phenylethylidene)-2-propyl-4H-imidazol-4-one-3-yl-methyl)-3'-methyl(1,1'-biphenyl-2-yl)sulfonyl carbamic acid n-butyl ester. 3.A pharmaceutical composition comprising a pharmaceutically suitablecarrier and a compound of claim
 1. 4. A method of treating hypertensionin a warm blooded animal comprising administering to an animal in needof such treatment an effective amount of a compound of claim
 1. 5. Amethod of treating congestive heart failure in a warm blooded animalcomprising administering to an animal in need of such treatment aneffective amount of a compound of claim 1.